CPAP Treatment and Cardiovascular Prevention: We Need to Change the Design and Implementation of Our Trials.

Abstract

Numerous studies have demonstrated the pathophysiologic mechanisms mediating adverse cardiovascular and cerebrovascular (CV) consequences of OSA. Further, large observational studies have shown that CPAP therapy reduces the CV burden of OSA.1 Yet, randomized controlled trials (RCTs) have failed to demonstrate the treatment efficacy of CPAP.2-4 In the largest trial (SAVE [ Sleep Apnea Cardiovascular Endpoints]),2 2,687 patients with OSA and established CV disorders were randomized to CPAP or usual care. After a mean follow-up of 3.7 years and a mean CPAP use of 3.3 h/d, the intention -to-treat analysis showed lack of benefit of CPAP therapy for the composite end point ( death from any CV cause, myocardial infarction , stroke , hospitalization for heart failure , unstable angina, or transient ischemic attack [TIA]). Similar results were obtained from a metaanalysis.5 These RCTs and metaanalysis,2-5 however, have had a number of pitfalls.6 Based on what we have learned from these studies, the objective of this commentary is to provide suggestions regarding the challenges in design and implementation for future well-thoughtout RCTs to address whether CPAP therapy can reduce OSA-associated CV risks .